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UNIVERSITY OF KENTUCKY
The Hays Report
The Hays Report
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The Hays Report
The Hays Report
The Hays Report
Effectiveness of Feed Additive Usage
of Antibacterial Agents
in Swine and Poultry Production
Virgil W. Hays
Edited version of Tlie Hays Report prepared for the Office of Technology
Assessment, United States Congress.
Published by Rachelle Laboratories, Inc., 700 He)ir\' Ford Avenue.
Long Beach, California 9080L
It was as true — as turnips is.
It was as true — as taxes is.
And nothing's truer tfian them.
Documentation of the benefits of feed additive antibiotics for swine and poultry
production is clearly needed by producers and feed manufacturers. Perhaps more
importantly, documentation of the benefits is needed, if feed additive antibiotic usage is
to be sustained against the seemingly constant regulatory pressures to ban their use. The
enclosed report presents a 30-year summary of "Effectiveness" of feed additive antibiotics
in poultry and swine production. It is a "Commissioned Paper" prepared by Dr. Virgil W.
Hays, University of Kentucky for the Office of Technology Assessment, Congress of the
United States. The poultry and swine industry is truly indebted to Dr. Hays for
accumulating, digesting, and organizing the mass of data contained in his report. The
use of feed additive antibiotics clearly continue to be beneficial in poultry and swine
V. C. Speer
Professor, Animal Science
Iowa State University
The author received his early train-
ing in Animal Sciences at Oklahoma
State University and the Ph.D. in
Animal Nutrition at Iowa State
University. He has held research
and teaching appointments at Iowa
State University and University of
Kentucky and presently is Professor
of Animal Nutrition and Chairman
of the Department of Animal Sci-
ences at the University of Kentucky.
Professor Hays has extensively
studied the effects of antibacterial
agents on performance of animals,
development and transfer of anti-
biotic resistance and tissue clearance
of antibacterial agents. He has writ-
ten extensively on the biological
effectiveness of antibacterial agents
and factors affecting their responses.
ABOUT THE AUTHOR vii
I. INTRODUCTION 1
II. MODE OF ACTION 3
A. Metabolic Effect 3
B. Nutrient Sparing Effect 3
C. Disease Control Effect 10
III. CONTINUED EFFECTIVENESS 21
IV. EFFECTIVENESS OF ANTI BACTERIAL AGENTS
IN SWINE FEEDING PROGRAMS 3 1
V. EFFECTIVENESS OF ANTIBACTERIAL AGENTS
IN FEEDING PROGRAMS FOR GROWING
CHICKS AND LAYER HENS 41
VI. EFFECTIVENESS OF ANTIBACTERIAL AGENTS
IN FEEDING PROGRAMS FOR TURKEYS 47
VII. EFFECTS OF ANTIBIOTICS ON MORTALITY AND
VIII. SUMMARY 51
IX. RESEARCH NEEDS 52
Antibiotic feed supplements have been extensively used in every major livestock and
poultry producing country for more than 27 years. In the United States alone, tiie non-
medical sales of antibiotics averaged 1.05 million kg annually between 1963 and 1972
(see figure 1 ).
PRICE AND SALES VOLUME OF ANTIBIOTICS
FOR NONMEDICAL USES
U.S. Tariff Comm. 1951 - 1972
Figure 1. Average price and total sales of antibiotics for nonmedical uses, 1951
In addition, substantial quantities of arsenicals and nitrofuran drugs are used. The wide
acceptance of antimicrobial agents is attributable to the known benefits of increased
growth rate, improved feed conversion and reduced mortality and morbidity due to
clinical or subclinical infections.
Antibacterial agents commonly used in swine and poultry production as dietary additives
include bacitracins, chlortetracycline, erythromycin, neomycin, oxytetracyciine, oleando-
mycin, penicillin, streptomycin, tylosin, arsenicals and nitrofurans. Recently bambermy-
cins and virginiamycin have been added to the approved list. Among those presently used,
some are more effective as growth promoters tlian others. Other antibiotics Iiave sliown
promise experimentally as effective additives; several which are not approved as feed ad-
ditives are used as therapeutic agents.
The total number of antibiotics approved for use in livestock and poultry production,
either as feed additives or for therapeutic usage, total about 14. This is a substantial
number; however, Raper (428) reported that some 300 antibiotics had been described and
partially evaluated by 1952; since then many others have been discovered and evaluated.
Therefore, only a small percentage of antibiotics available has been found to have major
application; the majority are unsuitable for one or more reasons, including low activity,
toxicity to the host animal, resultant tissue residues, etc. Some may be quite effective
but offer no particular biological advantage over those presently used; thus their develop-
ment on an industrial level cannot be justified. Though the quantity produced and sold
varies from year to year, about 40% of the antibiotics sold in the U.S. is for nonmedical
uses, mainly as feed additives (see figure 2).
TOTAL AND NON -MEDICAL SALES OF ANTIBIOTICS
U.S. Tariff Comm., 1949-73
Figure 2. Sales of antibiotics for medical and nonmedical uses, 1949 to 1973 (536).
It is widely recognized that antibiotics effective in improving the performance of animals
have one thing in common: the suppression or inhibition of the growth of certain micro-
organisms. Their chemical compositions and bacterial spectra vary widely. Some of the
effective antibiotics are readilv absorbed into the vascular systenijothers are barely ab-
sorbed. The chemical compositions, bacterial spectra and absorption and excretion pat-
terns of these products are clearly associated with their bactericidal and bacteriostatic
properties and effectiveness against specific systemic infections; however, these character-
istics are less readily associated with effectiveness as a routine growth promoter.
II. Mode of Action
For the growth-promoting activity of antibiotics, at least three modes of action have been
postulated, each with varying degrees of support: (a) The metabolic effect: The antibiotics
directly affect the rate or pattern of the metabolic processes; (b) The nutrient-sparing
effect : The antibiotics may reduce the dietary requirement for certain nutrients by stim-
ulating the growth of desirable organisms which synthesize vitamins or amino acids, by
depressing the organisms which compete with the host animal for nutrients, by increasing
the availability of nutrients via chelation mechanisms, or by improving the absorptive ca-
pacity of the intestinal tract; (c) The disease control effect: The suppression of organisms
causing clinical or subclinical disease, by inhibition of multiplication of organisms that
produce toxins, or by limiting their capacity to produce toxins which reduce performance
but result in no obvious symptoms of disease.
A. Metabolic Effect
The data which support the metabolic effect theory also tend to support a disease-
control effect, as the rate of metabolism may be influenced by systemic infections,
digestive upsets or absorption of microbially-produced toxins from the gastroin-
testinal tract. Metabolic reactions are influenced by antibiotics: Braude and Johnson
(65) reported that the feeding of chlortetracychne affected water and nitrogen
excretion and suggested that it may influence the metabolic rate of pigs; Brody
et ah (73), using rat liver homogentates, found that tetracyclines inliibited fatty
acid oxidation by the mitochondria. Weinberg (571) also showed that, in bacteria,
phosphorylation and oxidation reactions requiring magnesium ions were inhibited
by tetracyclines; and, Hash et al_. (207) demonstrated that tetracyclines inliibited
Numerous reports illustrate that antibiotics have metabolic implications, and that
bacteriostatic or bactericidal properties are associated with metabolic effects. How-
ever, in view of the nature of the animal responses, the normal tissue levels of the
antibiotics when added to the diet at growth promoting levels and the levels neces-
sary to mediate such biochemical responses, the metabolic effects cannot account
for the growth promotion in animals fed diets supplemented with moderate levels
of antibiotics. Furthermore, a direct metabolic effect should not vary greatly with
the environmental conditions as discussed in the subsequent section on disease
control effect. A direct metabolic effect could be consistent with variations discuss-
ed in the nutrient sparing section as nutrient levels at the site of metabolic reac-
tions could modify rate and extent of metabolic reactions.
B. Nutrient Sparing Effect
The nutrient-sparing effect has considerable research support. It is well recognized
that certain intestinal organisms synthesize vitamins and amino acids which are
essential and that other bacteria require and compete with the host animal for
these essential dietary nutrients.
Moore et al. (359) reported that streptomycin stimulated the growth or permitted
rapid growth of some yeasts; Anderson et al. (8) ifound that feeding diets containing
penicillin increased the numbers of intestinal coliforms other than Escherichia coli .
Such organisms synthesize nutrients that are dietary essentials; if a diet is deficient
in a specific nutrient, this deficiency could be partially corrected by microbial
synthesis and the specific nutrient subsequently made available for absorption by
the host through digestion of the microorganism or by other means of release of the
nutrient from the microorganism.
Other researchers report a depression in growth of organisms that are considered
competitive with the host animals for dietary needs. March and Biely (315) indi-
cated that the bacteria most affected by chlortetracycline were the lactobacilli.
Anderson et al. (9) and Johansson and Sarles (258) also reported that antibiotics
caused a reduction in the numbers of lactobacilli; Anderson et al_. (9) reported that
penicillin decreased the number of enterococci in the cecum of the chick. The
lactobacilli require amino acids in relatively proportionally similar amounts as chicks
and pigs; studies have shown that levels and sources of proteins which support
maximum growth in pigs are also near optimum for the multiplication of lactobacilli
in the intestinal tract (Kellogg et a[. 273a). Hence the bacteria can compete with
their host for essential amino acids not present or deficient in the diet. Though
these bacteria may later be digested, the site of digestion may be past the site of
optimal absorption. It has also been observed that those antibiotics most effective
in reducing the number of these organisms in the intestinal tract, thus reducing com-
petition for nutrients, are also the most effective as routine growth promoters
(Kellogg et ah 272). A reduction in populations of organisms which compete with
the host animal for the dietary essential nutrients may be beneficial, especially if
the levels of certain essential nutrients are critically low. Such mechanism of action
could partially explain the unusually marked responses reported for some experi-
ments in the early 1950's, when optimum levels of many of the essential amino
acids and vitamins were unknown.
Another type of nutrient sparing effect could be the improved utilization, parti-
cularly improved absorption, of the limited quantities of nutrients available to the
host animal. Catron et ah (99) reported an increased rate of glucose absorption in
animals fed rations fortified with antibiotics, thus providing evidence for the im-
proved nutrient utilization by improvement of the absorptive capacity of the in-
testinal tract. Coates (110) demonstrated that the gut wall was thinner in chicks
fed rations containing an antibiotic than the intestinal wall of chicks fed diets not
containing antibiotics. Rusoff et al. (433b) and Braude et al_. (64) observed similar
effects in calves and pigs, respectively. Coates also noted that feeding chicks the in-
testinal contents of infected chicks resulted in a thickening of the intestinal wall.
Similar effects of antibiotics on the thickness of the intestinal wall have been re-
ported by others (Coates et al.. Ill; Gordon, 184, 185a; Gordon et a[., 185b;
Hill et_al., 236; and Taylor and Harrington, 522). The thinner intestinal wall implies
a potential for improved absorption (Taylor, 521) and is assumed to be a result of
the inhibition of the organisms which produce toxins or of the production of toxins
which damage intestinal tissue. Improved utilization of nutrients due to a healthier
intestinal wall actually could be classed as reduction in subclinical disease or
inhibition of toxin production.
Catron et al_(98), Burnside et ah (83) and Beacom (30, 3 1) reported research which
suggested that the level of protein required by pigs for maximum performance was
less in the presence of dietary supplements of antibiotics. Tables 1 and 2 summarize
the response of pigs and chicks, respectively, to varying protein levels in the pre-
sence or absence of antibiotics and show that maximum gains may be obtained at a
slightly lower level of protein if antibiotics are present in the diet or expressed dif-
ferently; rate of gain is depressed more by low protein in the absence than in the
presence of the antibiotic.
EFFECT OF CHLORTETRACYCLINE ON WEIGHT GAINS OF PIGS FED
PROTEIN AT FOUR LEVELS^
Daily Gain (g)
Level Fed i
■^Units of feed per unit of gain.
^Percent protein in the diet for the weight periods initial to 68, 34 to 68 and 68 to
91 kg. body weight, respectively.
EFFECT OF ANTIBIOTICS ON THE RESPONSE OF CHICKS TO VARYING
^Summary of 4 experiments. West and Hill (574).
The eflect of protein level on response is more obvious in the chick data in Table
2. The optimum level of protein for chicks is about 20%. At or above that level,
chick weights were improved by 2.3 to 5.1%. Below that level, antibiotics im-
proved chick weights by 8.0 to 9.7%. Note similar effects on feed/gain.
Not only is there an interaction of antibiotics and level of protein (provided the
levels of protein tested include a definite sub-optimum level) but also there is an
interaction of antibiotics and the quality (amino acid balance) of protein. For
young calves and pigs, milk proteins are definitely superior to vegetable proteins
because the former are more readily digested and have superior amino acid balance.
An e.xample of the antibiotic x protein quality interaction is provided by Hogue
et a[. (240); the amount of milk in the diet of young dairy calves influenced tlieir
response to antibiotics. Though the growth rate of the calves was higher on the
higher levels of milk, the response to chlortetracycline was greater (11.3%) versus
5.1%) on the poorer quality (low milk) diet (Table 3).
EFFECT OF CHLORTETRACYCLINE ON GROWTH OF CALVES FED MILK
AT TWO LEVELS^
Level of Milk Fed
^Hogue et al_. (240).
Such diet x antibiotic interactions are reported for other species as well. From a
comprehensive summary of the effects of antibiotics on the performance of beef
cattle, Burroughs et al. (84a) also noted that animals on diets which resulted in
less rapid and efficient gains (lower quality or lower in available nutrients) showed
a greater percentage response to chlortetracycline (Table 4).
EFFECT OF CHLORTETRACYCLFNE ON WEIGHT GAINS OF BEEF CATTLE
FED HIGHER AND LOWER GAINING DIETS^
Diet and No.
Average Improve- Average Improve-
(kg) ment (%) ment (%)
Higher gaining diets (34 comparisons)
Fed Chlortetracycline 1 . 1 03
Lower gaining diets (3 1 comparisons)
Fed Chlortetracycline .681
^Burroughs et a].. (84a).
"Units of feed per unit of gain.
Lucas (304), Braude et al_. (66, 67), Stokstad (502), Burnside e^al_. (81 ) and others
presented evidence of an association between diet and antibiotic response. This re-
lationship can be seen in the change in response to antibiotics over years in Table 5.
RESPONSE OF PIGS TO ANTIBIOTICS DURING THE STARTER STAGE
(PIGS WEIGHING LESS THAN 35 POUNDS AT START OF TEST)
1. 01 1
1. 00 1
^Number of experiments and number of replications (pens) and pigs per treatment.
"Initial and final weight, lb.
'^Average daily gain and feed/gain for pigs fed diets without (-) and with (+) antibiotics
^Chlortetracycline and oxytetracycline. References: 22,23,36,55,79,98, 102, 107, 108, 127, 129,
147, 159, 216, 218, 220a, 242, 257, 259, 277, 294, 313, 426, 470, 494.
^References: 28, 108a, 123, 129,257,294.
fReferences: 32,33, 129, 147,247,257,277,284,298,398,434,494,538.
gPenicillin-Streptomycin. References: 34,35,36,55,68, 108, 147,255,257,350,398,408,427,
•^References: 3, 125b, 129, 147,257,285,343,347,348,395,396,424,434.
^Chlortetracycline, Sulfamethazine or Sulfathiazole, Penicillin. References: 3, 4, 103, 104, 108, 147,
157a, 157b, 159, 161, 200, 201, 202, 203, 217, 219, 238, 259, 277, 280, 284, 313, 333, 334, 341,
375, 386, 390, 398, 455, 494, 529b, 532, 546, 550, 551, 552, 589.
Ijylosin- Sulfamethazine. References: 108, 247, 333, 334, 335, 341, 386, 436, 494, 529b.
"^References: 3,4, 126, 147, 157a, 198, 201, 219, 341, 369, 385, 386, 390, 398, 435, 529b, 531, 532,
"References: 3, 199.
^References: 4, 20, 23, 24, 27, 108, 238, 425, 55 1 , 552, 549.
In the 1950"s most of the research with young pigs involved diets containing rela-
tively high levels of milk products, in more recent years, much of the research
effort has been devoted to improving performance on diets without milk, since milk
is considered too expensive to use extensively in pig starters. Thus, while no change
or a decrease in the response to antibiotics can be expected a higher level of response
in the starter stage since 1957 than prior to 1957 is seen. The response to antibio-
tics is generally greater if the antibiotics are included in an inadequate diet. This
response suggests an improved utilization of nutrients at critical or suboptimal
levels and can be ascribed to nutrient synthesis by intestinal organisms, reduced
competition from bacteria for critical nutrients or improved absorption.
Though there is substantial evidence that antibiotics will markedly enhance the
performance of animals fed a diet low in protein or inadequate in other nutrients,
there is evidence that the effect on nutrient utUization is indirect. Meade and
Forbes (332), Wallace et al. (565) and Bush et_ al_. (84b) presented evidence sug-
gesting that enhancement in growth was accompanied by an increase in food intake;
and though total nitrogen, calcium or other nutrients retained was greater, the
percentages retained by the two groups of animals (those fed antibiotics and those
not fed antibiotics) were similar. The increased feed intake accompanying re-
sponse to antibiotics may provide evidence that the response is not a result of a
direct effect on nutrient absorption or utOization; however, such evidence does not
detract from the practical benefits of antibiotics. The improved feed intake may
simply be a result of improved health resulting in improved growth rate and appetite,
thus leading to improved efficiency. Environmental conditions existing in most
balance studies (extreme cleanliness, one animal per metabolism crate, controlled
temperature, etc.) are not conducive to dramatic antibiotic responses. Studies per-
formed in more practical conditions in which feed intake was limited to a standard
level, as practiced in Europe, have shown that responses to antibiotics occur even
though feed intake is held constant. Data summarized by Melliere (336) illustrated
that pigs fed at a restricted level responded to tylosin (Table 6).
RESPONSE TO TYLOSIN IN PIGS FED A RESTRICTED AMOUNT OF
FEED PER DAY^'l^
Pigs per treatment
Avg. daily feed intake, g
Avg. daily gain, g
"Results of trials on commercial farms in Germany, England. Holland and Italy.
In the United States growing pigs, chicks and turkeys are normally allowed ad
lihitum access to food.
Tlie increased response to antibiotics in tlie presence of nutritional stresses is of
major economic significance in the production of meat, milk and eggs, since it is
often economically desirable or pragmatically convenient to feed nutrient sources
or levels which will not promote maximum rate of gain. In livestock and poultry
feeding programs, antibiotics may partially bridge the gap between optimum and
economically practical diets. More specifically, protein supplies may be too expen-
sive (as in the example of milk in pig starter diets) to permit the feeding of optimum
levels. Feed quality may also vary depending on growing, harvesting or storage
conditions. Such variations are beyond the control of livestock producers and can-
not be entirely corrected by diet formulation.
Disease Control Effect
Thougli there is extensive evidence of nutritive and antibiotic response relationships,
such effects appear secondary to the disease-control effect. Numerous studies sup-
port the conclusion that the major benefits derived from antibiotics as routine feed
additives result from the suppression or control of subclinical or nonspecific dis-
eases. Early in the history of antibiotics as supplements to animal feeds, it was
noted that the degree of response to antibiotics was inversely related to the general
well-being of the experimental animals. Speer el ai. (497) observed that healthy,
well-nourished pigs did not respond to antibiotic supplements when housed in
carefully cleaned and disinfected pens which had not been previously used. These
findings have been confirmed by other research with other species (Catron et_dL,
100; Coates et al., 1 12 and Hill et al., 234).
Studies involving both clean and contaminated environments illustrated that the
response was greater in contaminated or previously used environments. Bowland
(56) presented results of pig tests involving a new and an old barn. His data, sum-
marized in Table 7, show that antibiotics resulted in a 14.3% increase in growth
rate of pigs housed in the old barn; in the new barn, antibiotics resulted in only a
7.5% increase in growth rate.
EFFECT OF CHLORTETRACYCLINE ON WEIGHT GAINS OF PIGS
IN DIFFERENT ENVIRONMENTS^
(g) ment (7f)
"Units of feed per unit of gain. 10
Similar differences were noted for improvements in feed conversion in the new and
old barns. Bird et a].. (48) presented similar results with chicks. The response of
chicks to chlortetracycline in a new environment was 12.6% improvement in gains
during four weeks, as compared to 18.2% for chicks from the same hatch that were
reared in the previously used environment (Table 8). Coates et al. (1 12) reported
similar observations (Table 8).
RESPONSE OF CHICKS TO CHLORTETRACYCLINE (CTC) AND
PENICILLIN IN NEW AND PREVIOUSLY USED ENVIRONMENT
4 wk. Wt.
Previously used house
Coates, etal., 112^
^Reading Lab. had been previously used to house chicks but the Greenford Lab. had not.
In a previously used environment, penicillin increased gains by 23.9%; gains were
improved by only 1.6% in the unit not previously used.
Wachholz and Heidenreich (538) provided additional evidence that the cleanliness
or previous use of the environment affected the magnitude of the response to anti-
biotics (Table 9).
RESPONSE TO TYLOSIN BY PIGS HOUSED IN TWO
ENVIRONMENTS - NEW BARN VS. DIRT LOTS^
^Wacliholz and Heidenreich (538).
"Area had been used several years for rearing pigs.
'^l 10, 44 and 1 Img/kg., respectively for starter, grower and finisher diets.
They tested the growth promoting effects of tylosin in a new barn and in a dirt lot
facility which had been used for pigs for several years. The increased rate of gain
from supplementing the diet with tylosin averaged 2.4 to 14.6% in the new barn as
compared with 9.6 to 19% in the dirt lot facility, a less desirable environment. Ob-
viously new buildings cannot be provided for each batch of chicks or pigs, but such
data illustrate the need for improved sanitary practices.
Hays and Speer (216) conducted two field tests comparing the effectiveness of dif-
ferent levels of spiramycin (Table 10).
EFFECT OF SPIRAMYCIN AND TETRACYCLINES
ON WEIGHT GAINS OF PIGS FED IN TWO ENVIRONMENTS^
Level of Spiramycin
First environment^' "
Second environment ' §
"Unit of feed per unit of gain.
'^Building thorouglily cleaned and disinfected before test, occupied only by pigs in test.
64 pigs fed at each level, averaging 26.3 days of age and 5.63 kg. body weiglit, initially.
®50 g/ton of chlortetracycline or oxytetracycline in first and second environments,
Building not thorouglily cleaned before test and contained older pigs before and during
^59 pigs fed at each level, averaging 31.8 days of age and 5.69 kg. body weight, initially.
In one test, the building was emptied, thoroughly cleaned and disinfected before
st-^rting the test, and only those pigs involved occupied the buOding during the test.
The building used in the other test contained older pigs preceding and during the
test, and neither the building nor the individual pens were thoroughly cleaned or
disinfected before the test. In the cleaner environment, spiramycin (50 g/ton of
diet) resulted in a 33% improvement in gains and a 10.5% improvement in feed ef-
ficiency; in the uncleaned building, the addition of the same level of antibiofic to the
diet resulted in a 75%o increase in growth rate and a 37% improvement in feed con-
version. Similar responses to cWortetracycline (50 g/ton) and to oxytetracycline
(50 g/ton) were noted.
Lower levels of spiramycin resulted in lower response. Though other variables, such
as climatic conditions and breeding of animals, may have influenced the perfor-
mance, the relative contamination of the buildings obviously had an important
bearing on response to antibiotics. The buildup of a nonspecific infection in
buildings continuously used to house animals can depress performance of animals
without resulting in obvious symptoms of a disease problem. This is the kind of
problem for which routine feeding of antibiotics is useful and therapeutic use is not
Scott (449) presented an excellent example of the buildup of the growth depressing
effect of non-specific infections in a chick starting facility. The performance of suc-
cessive hatches of chicks of similar breeding and fed similar diets was poorer than
that of previous hatches (Table 1 1).
EFFECT OF A "NON-SPECIFIC INFECTION" ON CHICK GROWTH^
Hatch No. Avg. Gain 0-7 Days Relative Gain
^Adapted from Scott, 449.
Depopulation and fumigation
Emptying the facility, cleaning it thoroughly and fumigating it resulted in some
improvement in performance. However, even this did not result in a growth rate
of chicks approaching the level of performance of the first hatch. These are the
kinds of problems which feed additive usage of antibiotics help to control. Some
critics of antibiotic usage have suggested that the only need for antibiotics results
from housing pigs and chicks in filthy overcrowded houses. Such statements are
greatly exaggerated and suggest that the individuals are not acquainted with practi-
cal livestock and pouhry production. Even in the new house illustrations above,
there were responses to antibiotics. Furthermore, the most uninformed should re-
cognize that new facilities or complete isolation cannot be afforded for each far-
rowing of pigs or hatch of chicks.
Tlie challenge experiments of Miyat and Gossett (353) further demonstrated the pro-
phylactic effects of antibiotics in controlling specific diseases (Table 1 2).
EFFECT OF FEEDING TYLOSIN ON EXPERIMENTALLY INDUCED
HEMORRHAGIC DYSENTERY IN PIGS^
Amount of Tylos
^Miyat and Gossett (353).
Units of feed per unit of gain.
^Antibiotic included in water for 6 to 8 days before infection and for 4 or 5 days after
"40 g/ton of feed after water treatment
^100 g/ton of feed for 2 days before and for 33 or 15 days after infection, followed by
Treatment with tylosin was effective in controlling hemorrhagic dysentery, hut
treatment followed hy prophylactic administration of the antihiotic was more ef-
fective in restoring performance to normal. These data illustrate the marked im-
provement in performance resulting from antihiotic supplements in severely high
and, in this case, specific disease conditions. Similar ohservations have been re-
ported on naturally occurring outbreaks of hemorrhagic dysentery (Gossett and
Braude e^'d[. (67) summarized a large number of experiments and concluded that
the relative improvement in growth rate resulting from supplementing the diets with
antibiotics was inversely related to the growth rate of the control animals (Table 1 3).
RELATIONSHIP BETWEEN GROWTH RATE OF CONTROL ANIMALS AND
ANIMALS FED ANTIBIOTICS^
in Weight (g)
No. of Tests
^Adapted from Braude eta[. (67).
Similar experiments, involving the antibiotic combination of penicillin and strepto-
mycin and conducted about ten years after the studies by Braude et al_. are sum-
marized and presented in Table 14.
RELATIONSHIP BETWEEN GROWTH RATE OF CONTROL PIGS
AND PIGS FED A COMBINATION OF PENICILLIN AND STREPTOMYCIN^
Daily Gain In
Improvement Over Controls By
Pigs Fed Antibiotics
Weight of No. of
Controls (g) Comparisons
91 to 182 2
182 to 272 3
272 to 363 4
363 to 454 7
454 to 545 9
545 to 636 9
636 to 726 20
Average Improvement, %
^Data summarized from agricultural experiment station reports, 1960 to 1967 (212a).
Of 61 comparisons included in the summary, 56 showed a positive response in feed
conversion, with average improvements of 10.7% and 5.1% for rate of gain and feed
As mentioned earlier, the observation that degree of response is associated with
degree of contamination has led to the suggestion that antibiotics are being used as
a substitute for good housekeeping and sanitation procedures. There are practical
and economic limits which can be made by livestock producers in sanitation
procedures. Experiment stations, which usually employ husbandry and sanitation
practices beyond the practical limits of producers, do, nonetheless, note responses
to antibiotics of substantial magnitude.
The data used to estimate the economic benefits from the use of antibiotics are for
the most part based on experiments conducted at experiment stations. Most of the
data used in estimating benefits to poultry is based on performance of chicl<s in
batteries. Experiment station researchers employ management and sanitation pro-
cedures that are difficult, or nearly impossible, and certainly often impractical for
the producer. For example, many of the tests involve only healthy pigs at the be-
ginning; however, the farmer must rear all of liis pigs. The exaggerated response
to antibiotics by unthrifty (runt) pigs is illustrated by a number of experiments,
some of which are summarized in Table 15.
VALUE OF CHLORTETRACYCLINE FOR UNTHRIFTY PIGS^
As Percent of Controls
Exp. ADG F/G
1 203 79
2 184 79
3 315 63
4 215 76
5 121 87
6 151 86
7 186 78
8 161 86
9 149 83
10 173 69
11 300 71
Avg. 196 77
^Braude et d. (67).
Researchers normally cull out this quality of pigs prior to starting the experiments.
Note that antibiotics resulted in a near doubling of tlie growth rates and improved
feed efficiency by an average of 77%. These studies are included in the upper part
of Tables 13 and 14. Sainsbury (439) also presented an excellent example of the
difference in response of normal healthy pigs and those he classed as "bad doers"
or what we frequently term as "runt" or "unthrifty" pigs. Antibiotic supplements
to the diet of the noimal pigs resuhed in a 10% improvement in rate of gain; anti-
biotic supplements to the "bad doers" resulted in a 30% improvement in gains.
Thus, if unselected pigs are used (as the producer must), a greater response to
antibiotics is expectable than if only healthy pigs are selected.
Also, researchers usually clean the facility well and the facility may be idle between
groups of pigs or chicks. This practice should result in a lesser response to antibio-
tics as illustrated in Table 10. It is difficult or nearly impossible to thorouglily
clean and sanitize many swine facilities.
Another procedure commonly followed in many experiments which undoubtedly
reduces the stress on animals and hence reduces the expected response to antibio-
tics is the practice of using only a few animals per pen. In fact, some of the antibio-
tic studies involve single pigs per pen; most involve only 4 to 6 animals per pen. It
is obvious that this is not a practical management procedure. It is common practice
to have 75 to 100 or more pigs per pen. Many chick and turkey experiments in-
volve 10 or fewer birds per pen and often in wire floored batteries; in practical
production, hundreds may be housed per pen.
Melliere et a].. (338) summarized 69 swine experiments conducted under research
station and farm conditions and verifies that the average response is greater in the
farm situation. Their data are reported in more detail by Natz (374) and sum-
marized in Table 16.
EFFECT OF TYLOSIN ON GROWTH RATE
AND FEED CONVERSION OF FINISHING PIGS^
Average daily gain
Research type I*'
Research type 2^
Research type I''
Research type 2'^' ^
^Meniere (338) and Natz (374).
Closed herds, confinement houses thoroughly cleaned prior to test.
'^Herd status and cleaning procedures not defined.
Practical production units.
^Feed/gain data available on only 16 of the 22 experiments for which rate of gain data
The average response for rate of gain and feed/gain was 5.7 and 4.7, respectively in
field trials as compared with 3.6 and 3.3 for University Experiment Station tests.
In experiments carried out in faciUties in which extreme care was taken to maximize
sanitary conditions, the response was 1 .7 and 0.3% improvement in gain and feed/
gain, respectively. Table 17 also presents a summary of differences in response to
antibiotics in practical and experiment station environments, summarized from the
observations included in Table 5.
RESPONSE TO ANTIBACTERIALS (STARTER PIGS)^
Location A.D.G. F/G
32 Field tests 28.4 14.5
128 Exp. Sta. tests 16.9 7.0
^Summarized from data included in Table 5 and based on
experiments involving 12,000 pigs. The antibacterials tested
include tetracycline, tetracyclines in combination with penicillin
and sulfamethazine, carbadox and the combination of tylosin
Note that in field conditions the response to antibacterial agents is nearly double
that observed for experiment station conditions. Thus, if the economic benefits
are calculated from the use of antibiotics on data from experiments in the field,
rather than from experiment station data, such benefits would greatly exceed the
533 million dollar estimate of Gilliam and Martin (181) for economic returns to use
of antibiotics in swine production.
It has been suggested that there is no need for feed additive usage of antibiotics if
one has a Specific-Pathogen-Free (SPF) or Minimal Disease (MD) herd. SPF and MD
are terms used in the U.S. and Great Britain, respectively, to designate animals that
are free of mycoplasma pneumonia, atropliic rhmitis and possibly other diseases
that are spread by direct pig to pig contact. Any reduction in disease should lower
the response to antibiotics. However, there are many experiments which illustrate
that SPF pigs respond to antibiotics. Much of the data available has been sum-
marized by Hays (211), and indicates that there is little difference in responses to
antibiotics by SPF and non-SPF pigs used in experiment station research. Sainsbury
(439) also reported that MD pigs fed antibiotic supplemented diets grew 8% faster
than their respective controls as compared with a 10% improvement for conven-
tional pigs supplemented with antibiotics. Every practical method should be
utihzed to reduce the morbidity and mortality from disease; however, at present
there are no methods available that would contraindicate the need for feed ad-
ditives. The wise use of antibiotics is not a substitute for but complements good
husbandry, sanitation and disease control practices.
III. Continued Effectiveness
The extensive use of antibiotics as feed additives has elicited concern about potential
harmful effects due to the development of resistant strains of organisms in the host ani-
mal or due to resistant organisms or allergic reactions in the consumer of the meat, milk
or eggs from animals continuously fed antibiotics. Concern should exist with the appHca-
tion of any new drug either as a feed additive or a medicament; but, after 27 years of
usage of some of these drugs, fear should have changed to rational thinking leading to ade-
quate evaluation of the potential harmful effects as contrasted with the proven health and
After more than 27 years of extensive use of antibiotics in animal feeds, discussions still
deal with "potential" public heahh hazards, as did a presentation 16 years ago (Goldberg,
183). Significantly, it is difficult to cite a single human health problem that can be at-
tributed to the consumption of meat from animals fed antibiotics or that can be associated
with direct or indirect contact with animals fed antibiotics.
It has been well established that continuous exposure of enteric organisms to an anti-
biotic permits the development of strains of organisms with greater tolerance for or com-
plete resistance to that antibiotic. This is more readily demonstrated in laboratory tests
(in vitro) with pure cultures than it is with the complex microflora which exists in the
environment or in the gastrointestinal tract of domestic animals. However, an increase in
multiple and transferrable drug resistance has been observed in naturally occurring enteric
organisms from the use of antibiotics as feed additives (Smith et al., 485, and others).
The evidence that resistant organisms in animals compromise treatment of diseases in
man or animals is indirect and difficult to evaluate. For those persons concerned only
with disease treatment, the idealistic decision is to strictly limit the use of any drug to
treatment of a patient now or a "potential" patient in the future. For those who are
concerned with a healthy population and a plentiful food supply, which involves
both disease protection and efficient food production, the decisions are more complicated.
A thorough evaluation of the human health implications of any biologically active drug
is essential. When there are benefits, that is when there is some biological activity, there
are likely to be some risks involved. A more thorougli discussion of the risks or potential
risks of feed additive usage is covered in other papers.
It has been suggested that antibiotics are losing their effectiveness and that ever higlier
levels are being required to give the typical antibiotic response. The general explanation
for this is that the problem organisms are developing or have developed resistance to the
antibiotics. It is recognized today that 40 to 50 g/ton of a broad spectrum antibiotic is
normally required to approach a maximum response, whereas the generally recommended
level in the 1950's was 10 to 20 g/ton. However, the data of Catron et al. (100) illustrate
that, since antibiotics were first used, the recommended feeding level has not necessarily
been the level which would elicit maximum response. Even though a response was obtained
with 10 to 20 g/ton (Table 18), maximum gain was approached at 40 g/ton, and maxi-
mum feed efficiency was realized only at 80 g/ton, the higliest level tested.
EFFECT OF CHLORTETRACYCLINE FED AT DIFFERENT LEVELS
ON PERFORMANCE OF GROWING-FINISHING SWINE^
Level of Chlortetracycline
Per Day (g)
Feed required per unit gain.
Braude, et al.. (67) reported in 1953 that more than 20 g/ton of tetracycline or penicillin
was required for maximum response. Excluding experiments involving inadequate diets
or runt pigs, the percentage responses to tetracycline were 15.2 and 18.6 and to penicillin
were 9.1 and 13.1 for below and above 20 g/ton, respectively. These observations were
based on 125 tetracycline experiments and 45 penicillin experiments.
The levels selected for practical use are not necessarily the levels that will elicit maximum
response. The growth response increases with increasing levels of antibiotics, up to 250
g/ton or more in some cases. The rate of increase in growth response decreases, however,
as the level of antibiotic increases; thus, the level selected in practice is usually a com-
promise based on the cost-benefit ratio.
Improved methods of producing antibiotics and competition among producers have
resulted in a decline in the price of the commonly used antibiotics, which allows consider-
ation of the use of higher levels. Figure 1 presents price data for all antibiotics combined
and Table 19 presents the specific price liistories of penicillin, streptomycin and tetracy-
APPROXIMATE PRICE PER KILOGRAM OF FEED-GRADE ANTIBIOTICS
FOR THE SPECIFIED YEARS, 1950-1975
The prices of feed-grade penicDlin and streptomycin in 1975 were only 10 to 15% of the
1950 price and tetracycHnes were only about 20% as expensive as in 1950. These reduc-
tions in antibiotic prices were accompanied by increases in most other production costs.
The evidence available suggests that the decrease in cost of antibiotics per gram and the
increase in other production costs have been the primary reasons for higher levels being
recommended and used rather than any decline in effectiveness. The higlier levels were
more effective from the beginning; but, with the natural biological phenomena of a de-
creasing rate of increase with an increasing level, the practical optimum level changes
with cost changes, not only of the antibiotics, but other production costs and in addition
change with the market prices received for pigs. Prices of certain antibiotics have
increased within the past five years. These have essentially attained basic commodity
status (patent protection is gone for the older ones) and prices will respond to ingredient,
labor, transportation and other routine production costs. Removal of the older antibio-
tics from use in livestock production will increase cost of production, as it will force the
use of drugs that still are covered by patent protection in addition to removing some of
the most effective in terms of improving rate and efficiency of gain.
Certainly, there are tests in which little or no response is observed to a recommended
level of an antibiotic. This situation is not peculiar to the present. Similar observations
have been reported since the early use of antibiotics as dietary supplements. Speeret ah
(497) reported that 10 to 20 g of chlortetracycline per ton of diet did not improve the
performance of pigs in one test and suggested that the low disease level could be the
reason for lack of improvement.
Teague et a[. (523) reviewed the antibiotic studies conducted at the Ohio Station between
1950 and 1963. Variations were noted in the response from year to year, but there was
no consistent decline in antibiotic response. A similar study of the swine data from the
Iowa Station, 1950 - 1959, suggests that less response to antibiotics existed (Figure 3)
19 53 1954
INITIAL Wt. (lb) RANGE: 16-55 (Av. 29), FINAL Wt. 44-110 (Av. 77)
ANTIBIOTICS: OXYTET, P, B, P-B, P-S, OLEANDO, CHLORTET — B-P. STREPT
Figure 3. Response of growing pigs to antibiotics (V. C. Speer, Animal Science
Department, Iowa Agric. and Home Econ. Exp. Sta.)
A critical evaluation of the experiments conducted during those years shows that few were
performed and usually involved individually fed pigs in experiments designed to study the
effects of antibiotics on protein or vitamin utilization. The disease stress on the animals was
thus minimized as most of the animals were individually penned in metabolism cages.
Peo (397) summarized the long-term effects of antibiotic feeding to swine at the Nebraska
Station and concluded that, after more than ten years of extensive use of antibiotics, a re-
sponse was still being observed. His observations are particularly relevant, since, in that
period of time, the Nebraska researchers had changed to a "specific pathogen-free"herd
and had strived to keep disease conditions at a minimum.
Hvidsten and Homb (250) reported the results of 9 consecutive experiments on one farm
in which oxytetracycline and chlortetracycline were tested at low or high levels. Tlie
antibiotic-fed pigs gained 5% faster on the average for the 9 trials and the average im-
provement for the 9th trial was 5.3%. The lowest response to antibiotics was observed in
the 4th trial and the liigliest in the 5th trial, suggesting that the variations in results was
largely a result of normal variation associated with small experiments, and not a reflection
of a changing response to antibiotics.
To evaluate the continued effectiveness of tetracycline and the combination of tetracy-
cline, penicilHn and sulfamethazine, the data in Table 5 were statistically analyzed. The
differences between control and treated groups were liigWy significant (P<.01 ) for average
daily gain and feed required per pound of gain, for both the tetracycline experiments and
the experiments involving the antibiotic combination. For the tetracycline experiments
the predicted difference was 0.10 lb/day increase in rate of gain and a reduction of 0.12
lb. of feed per pound of gain as a result of having the antibiotic in the diet. There was no
evidence of a reduced effect with successive years of use. The predicted improvements in
rate of gain and feed conversion were 1 1.3% and 4.6%, respectively, as compared with the
observed values of 10.8% and 6.2%. The predicted differences were adjusted to a common
initial weight (17.4 lb.) and equal time on experiment (40.4 days).
For the experiments involving the combination of antibiotics, there was evidence of a
year by treatment interaction. A plot of the data showed an improvement with time in
rate of gain for the controls followed by a leveling or dropping off, with little or no
change in the performance of the treated group. The difference between controls and the
treated group was highly significant (P<.01). There was no evidence of a year by treat-
ment interaction for feed/gain ratios with a constant difference of 0.17 lb. less feed per
pound of gain for the treated group. The predicted improvement in feed conversion was
7.6% as compared with the observed average of 8.5% in Table 5. The predicted values are
adjusted to equal initial weights (18.4 lb.) and to equal time on experiment (36.2 days).
Tlie statistical analysis of each of these sets of data supports the conclusion that tetracy-
cline or the combination of tetracycline, penicilHn and sulfamethazine is still effective in
improving performance, with little or no evidence of a decline in effectiveness with time.
Similar questions have been raised about the continued effectiveness in poultry. Bird
(46) summarized data from 1951 to 1968 on birds taken from hatching to broiler weights
and concluded that the trends did not indicate a decrease in effectiveness. Table 20 pre-
sents a series of trials from 1964 to 1976 in which penicillin was used as a standard in
screening tests (Kiser, 273b).
SUMMARY OF CHICK RESPONSE TO PENICILLIN^
Gain (g) F/G
n Diet ^
'~( Improvement over Basal
Gain + S.E.M.
17.5 + 1.71
1 1.3 ± 1.66
13.4 + 0.68
16.4 + 0.86
13.0 + 2.19
9.3 + 1.36
6.5 + 0.47
7.6 ± 0.37
Each experiment contained 2 replicates of 10 birds each (5 males, 5 females). Trial lengths were
20 days for 1964 to 1967, 19 days for 1968 to 1971 and 13 days for 1972 to date.
''Penicillin was present at 180 g/ton of diet.
After 12 years of continuous testing in the same laboratory, penicillin still results in sub-
stantial improvements in performance. The percentage increase is lower in recent years,
but the overall performance of the birds has improved, particularly feed efficiency. It
should be noted that the length of test period has changed from 20 to 13 days (see foot-
note b). If one corrects for normal day-old weights, the rate of gain is equal to or superior
in the first 13 days in 1976 as it was for the first 20 days in 1964 The change is greater
for the controls than for the penicillin treated, another indicatic-" ihat the reauction in
percentage improvement due to antibiotics is a result of improved performance of con-
trols rather than a regression of the penicillin treated birds. Waibel et al. (556) titled a
% of Controls
paper "Disappearance of a Growth Response in Chick to Dietary Antibiotics in an Old
Environment." Heth and Bird (223) summarized the data from the same laboratory used
by Waibel et a[. but over a longer period of time and found the average responses to be
similar for 1950-53 as compared with 1956-59 (Table 21).
GROWTH RESPONSE OF CHICKS TO ANTIBIOTICS
FROM 1950 to 1961^
Tetracycline, 10-35 ppm
Penicillin, 4-30 ppm
Zinc Bacitracin, 10-35 ppm
1956-1959 16 105.9
Zinc Bacitracin, 100 ppm
^Heth and Bird, 223.
Heth and Bird (223) and Libby and Schaible (296) reported that in a given environment
the growth response of chicks to an antibiotic may be reduced but noted that the general
level of growth increased during the time period, leading the authors to conclude that
antibiotics had reduced the number of harmful organisms in the environment so that the
control chicks grew better, rather than the antibiotic fed birds regressing to the control
Tlie improved performance of controls with time should not all be attributed to a reduc-
tion of suppressive organisms; genetic and dietary progress has also been made. The im-
provement in diets should also result in a decrease in percentage response to antibiotics
as discussed in the section on mode of action. Other than the instance cited above of
using penicillin as a control drug in screening tests (Table 20), the continuous use of a
single antibiotic has not been critically evaluated, as it is not general practice for a live-
stock producer or a researcher to feed antibiotics throughout the animal's life cycle or to
use the same antibiotic year after year. However, numerous experiments have been
carried out that shed some light on whether the more commonly used antibiotics are con-
tinuing to improve the performance of animals. Elliot and Johnson (I 57b) conducted
several experiments on a single commercial swine farm over a period of six years. A sum-
mary of their evaluation of a combination of chlortetracycline, penicillin and sulfametha-
zine is presented in Table 22.
EFFECT OF FEEDING ANTIBIOTICS ON WEIGHT GAINS OF SWINE,
IN TESTS ON A SINGLE COMMERCIAL FARM, 1960-1965^'''
ige Daily Gain
^Elliott and Johnson (157b).
Antibiotic: 100 g. of clilortetracycline, 100 g. of sulfamethazine and 50 g. of penicillin
per ton of diet for pigs 3 to 9 weeks of age.
^ Units of feed per unit of gain.
This svnne producer had routinely fed diets containing chlortetracycline, but not penicillin
and sulfamethazine, during the entire period. Other antibiotics may have been fed inter-
mittently for short periods. The average performance and the response within any one
year varied probably as a result of the environmental conditions, including stresses, exist-
ing at the time the experiment was conducted. But, after six years of testing, tlie com-
bination of chlortetracycline, sulfamethazine and penicillin resulted in a 32% improve-
ment in rate of gain and an 18% improvement in feed efficiency.
Hays (211b) conducted an experiment on the same commercial swine farm that Elliot
and Johnson used. The results of that experiment are presented in Table 23.
EFFECT OF FEEDING ANTIBIOTICS AT HIGH LEVELS
ON WEIGHT GAINS OF YOUNG PIGS
Clilortetracycline-sulfamethazine -peni- 250
Penicillin-streptomycin'^ '^'"'" 100
^V. W. Hays (unpublished data, experiment 6443, Iowa Agr. Home Econ. Exp. Sta., 21 lb).
Average initial weight of pigs, 8.67 kg.; 4 pens of 10 pigs each per treatment, 34 days on test.
Pigs nursed sows prior to going on experiment.
''Unit of feed per unit of gain.
1:3 ratio of procaine peniciUin to streptomycin.
^100 g. of clilortetracycline, 100 g. of sulfamethazine and 50 g. of penicillin per ton of diet.
The response to the antibiotic combination was similar for the two studies: an improve-
ment of 32% and 34% in growth rate and an improvement of 16% and 18% in feed con-
version for the two tests conducted in 1965 (Tables 22 and 23). Table 23 also shows a 7%
improvement in feed conversion and a 25% improvement in rate of gain resulting from
the addition of chlortetracycline, thougli it had been used extensively on the farm for at
least five years. Tlie combination of penicillin and streptomycin resulted in similar im-
provements in performance.
The results of similar tests using tylosin from 1959 to 1966 are summarized in Table 24
EFFECT OF FEEDING TYLOSIN FOR A PROLONGED PERIOD
ON WEIGHT GAINS OF PIGS^
Average Daily G
100 g. of tylosin per ton of diet, except for last 2 lines in which the level of tylosin was 40g/ton.
The rates of gain and feed conversion by the animals in the later experiments were less
than in the earlier years, which Jordan attributes to change in the management program
and use of a more simpHfied diet which contained little or no milk products. The per-
centage of response is actually greater in 1965-1966 as compared with 1959-1962, in
keeping with the previous examples of an increased response for animals under nutritional
Hays and Baker (2 12b) conducted an experiment specifically to test the response to chlor-
tetracycline in a confinement svvane unit in which the antibiotic had been continuously
used for more than three years. The unit housed 650 to 700 pigs continuously for the
three-year period, which would allow ample time for resistance problems to develop.
Though the resistance patterns of the intestinal organisms were not determined we can
state with confidence, from our present knowledge of antibiotic resistance, that the in-
testinal coliforms were solidly resistant to tetracyclines and that resistance was a multiple
and transferable type. As illustrated in Table 25, chlortetracycline (50 g/ton) resulted in
a 10.2% improvement in growth rate and a 1.0% improvement in feed efficiency.
EFFECTS OF CHLORTETRACYCLINE ON WEIGHT GAINS OF PIGS
AFTER CONTINUED USE=^' ^
Daily Improve- Feed Improve-
Group Gain (g) ment (%) Efficiency^ ment (%)
Control (36 pigs) 577 2.97
(35 pigs) 636 10.2 2.94 1.0
^Hays and Baker (212b).
Chlortetracycline had been used continuously in the building for 3 years before the test,
and pigs had received chlortetracycline before the start of the experiment.
^ Units of feed per unit of gain.
^^50 g. of chlortetracycline per ton of diet.
A thorough evaluation of available data suggests that those antibiotics found to be effec-
tive as feed additives in the 1950's are still effective in the 1970's. The magnitude of the
response varies from experiment to experiment; caution must be used in basing con-
clusions on one experiment. Such a cautionary statement should not be necessary for a
researcher in biology, but normal biological variation may not be well understood by
those not experienced in conducting animal experiments and in the principles of bio-
statistics. Such variability may not be appreciated by those researchers who are ex-
perienced only in in vitro work in which greater control of the environment can be ac-
IV. Effectiveness of Antibacterial Agents in Swine Feeding Programs
Tables 5, 26 and 27 present a summarization of data from journal articles, field day re-
ports and unpublished data secured through private communications from research
RESPONSE Ob' PIGS TO ANTIBIOTICS DURING THE GROWER-DEVELOPER STAGE
(35 TO 1 25 POLINDS BODY WEIGHT)
WEIGHTED A VG.
^Number of experiments and number of replica lions (pens) and pigs per treatment.
Initial and final weight, lb.
^■Average daily gain and feed/gain for pigs fed diets withoiii (-) or with ( + ) antibiotics.
'^Chlorietracycline and oxytetracycline. References: 24, 26, 27, 28, 30, 34, 37, 38, 45.50,57,72,80,82,83.97, 130,
147, 154, 191, 205, 219, 220a, 221, 222, 246, 255, 256, 294, 302, 306, 343, 347, 349, 350, 375, 398, 409, 423, 425,
427. 494, 497, 498, 525, 530, 540, 543, 547, 548, 553, 563, 579, 93, 102, 1 26a, 227.
•^References: 34, 55, 72, 120, 130, 255, 256, 279, 347, 356,408,427, 494, 524, 5 79.
'References: 34. 35. 191, 220b, 265, 279, 280, 335, 343. 347, 375. 380. 398.409,427.434. 553. 579.
^References: 26,28,34,35, 153b, 191 . 2 14. 262a, 285. 302. 343, 345, 347. 380, 425,434.
' Chlortetracycline, penicillin and sulfamethazine or sulfathiazolc. References: 2, 4, 103. 220b. 278. 356. 357. 375. 380,
385, 408, 529b, 589, 344, 457.
J Tylosin-sulfamethazine. References: 344,408.
References: 4. 298. 375, 380, 38 1 . 494. 529b, 213.
RESPONSE OF PIGS TO ANTIBIOTICS DURING THE GROWING-FINISHING STAGE
(TESTS CONTINUED TO MARKET WEIGHT)
'■' I nip.
''Number ofexperiments and number of replications (pens) and pigs per treatment.
'''Initial (I) and final (F) weights, lb.
''Average daily gain and feed/gain for pigs fed diets without (-) or with ( + ) antibiotics.
^Combination of penicillin and streptomycin. References: 55. 137. 147. 180. 221, 254. 256, 265. 280. 398. 408.
^References: 69, 117. 120, 129.256,279,356,385,398,408,494,524.589.
'"Chlortetracvcline and o.xytetracycline. Retm-nces: 21 . 26. 28, 31 , 39, 51, 55, 71. 72, 80. 83,98, 100, 129, 173,
187, 191, 196, 202, 205, 215, 220a, 221, 222, 239, 246,255,291,294,302.343,375,398.402,409,437,494,
541, 542, 543, 547, 548, 553, 564, 565, 579, 590, 594, 70, 75, 77, 121.
gReferences: 129, 221, 265, 280, 291, 335, 343, 375, 398, 408,409, 529b, 553, 5 79, 589.
''References: 335, 341 , 356, 375. 408, 494, 547.
' References: 26,28, 129, 191.214,285,302,343.
J Includes arsanilic acid and 3-nitro-4-hvdroxv phenvlarsanic acid and experiments for all stages of production.
References: 24,37,69,78, 108a, 127, 204, 210, 294', 375, 398, 425, 494, 175.
•^References: 25, 391.
Efforts were made to omit data from studies in which nutrient deficiencies were involved.
For example, some of the earlier studies with antibiotics were designed to evaluate the
feed grade sources of antibiotics as contributors of both the antibiotic and "animal
protein factor" or vitamin Bi2- Studies that involved feed ingredients such as raw
soybeans, which exaggerate the antibiotic response, were also excluded. Those studies in
which the animals were fed individudly in metabolism cages were excluded as these
represent an abnormal situation in which little or no response to the antibiotic can or
should be expected. In addition, the data are primarily limited to experiments conducted
in the United States. Since management and housing practices as well as diets and feeding
management differ from country to country and these affect the response to antibiotics,
it is deemed advisable to emphasize U.S. data.
The average responses to the individual antibacterial agents or commonly used combina-
tions are presented in the upper part of the tables; for some, the results are reported by year
periods (1950-56, 1957-66 and 1967-77) in the bottom part of the tables. The three
tables cover the three stages of production for which it is a common practice to make
ration changes: starter (Table 5), grower (Table 26) and finisher (Table 27).
AD researchers do not follow the same procedures; it has been necessary to make some
arbitrary decisions as to which experiments to include in each summary. Table 5 includes
those experiments in which pigs weighed less than 35 pounds initially and were continued
on the diets to a maximum weight of 75 to 80 pounds. The summary for the grower
phase (Table 26) includes those experiments in which pigs weighed more than 35 pounds
and were continued on experiment until they weighed 125 to 150 pounds. The growing-
finishing summary includes data to market weight (Table 27).
As is commonly observed, the responses are much greater during the starter phase and
decline as the pig matures. This is particularly noticeable if the differences are expressed
as a percentage of the controls. For example, the differences between controls and pigs
supplemented with antibiotics in mean daily gain for all experiments is 0.14 pounds per
day for both the starter and the grower phase (Table 5 and 25). However, when expressed
as a percentage of the mean daily gain by control pigs, the 0.14 represents 16.09% improve-
ment during starter phase and 10.69% improvement during the grower phase.
It is obvious from the results presented in the tables that all antibiotics are not equally
effective for swine. Even though a drug may be approved by the Food and Drug Adminis-
tration as an additive to improve rate and efficiency of gain, there is no required assurance
that it be equally effective or superior to the previously approved antibacterials. Similar
differences in responses were reported in 1953 by Braude et al. (Table 28) and in 1954 by
Lasley et al. (Tables 29 and 30).
GROWTH AND FEED EFFICIENCY IN DIETS OF GROWING-FINISHING PIGS
FED DIETS FORTIFIED WITH VARIOUS ANTIBIOTICS ^
^Adapted from Braude et al, 67.
RESPONSE BY WEANLING PIGS FED ANTIBIOTICS IN DRY LOT^' ^
^Includes experiments in which pigs were fed to near 200 pounds body weight.
^Adapted from Lasley et al. (289).
EFFECTS OF ANTIBIOTICS ON PERFORMANCE AND SURVIVAL
OF GROWING-FINISHING PIGS^
Pigs ADG F/G
Avg. daily gain & avg. feed/gain
^Adapted from Lasley et al. (289).
It is obvious from these summaries that antibacterial agents are not equally effective in
improving growth rate and feed efficiency. In general, those of a broader antibacterial
spectrum (singly or in combinations) are more effective.
Copper sulfate is used extensively in Great Britain as a feed additive and has been tested
thoroughly in this country. When copper sulfate is added at a dietary level of 250 pprn of
elemental copper, an additive effect of antibiotics is usually not observed, indicating a
similar mode of action for the copper and antibiotics. Petitions to our regulatory agencies
for similar use in this country have not been approved, with certain concerns being
expressed about increased copper levels in tissues and adding excess copper to the environ-
ment. These are complicated and debatable issues and beyond the scope of this paper. The
experimental work on effects of copper on growth rate and feed conversion has been
thoroughly reviewed by Braude (63) and is summarized in Tables 31 and 32. As with anti-
biotics, there are variations among reports on the actual magnitude of rate of gain and
feed/gain responses. In Braude's review, the average improvement in rate of gain was 8.7%
and for feed conversion, 6.6% when copper (250 ppm) was added to the diet. Lower
levels of copper resulted in responses of a lower magnitude (Table 31).
RESPONSE OF PIGS TO VARYING LEVELS (PPM) OF DIETARY COPPER^
Improvement in Performance, %
Average Daily Gain
^Adapted from Braude (63).
The average responses for 1955-1965 and 1965-1975 were quite similar (Table 32).
EFFECTS OF COPPER (250 PPM) ON PERFORMANCE OF PIGS^
^Adapted from Braude (63).
It is obvious that some of the gains in production efficiency attributed to antibiotics
could be achieved by the use of other antimicrobial agents such as copper compounds,
arsenicais, nitrofurans and carbadox; however, the trade-offs in absolute efficacy or safety
have not been thoroughly researched or discussed. Restricting the use of one or a few
agents will naturally result in greater use of those not similarly restricted. The use of
other agents, which have not been thoroughly evaluated over an extended period, may be
more detrimental than the concerns presently being expressed about tetracyclines and
There is ample evidence that species, age of animal or stage of production, adequacy of
diet and environmental conditions are all important factors affecting the response to anti-
biotics. Each of these factors must be considered when selecting an antibiotic to use, level
to feed and duration of feeding. The examples in the sections on "Mode of Action" and
"Continued Effectiveness" will serve to illustrate effective application in feeding programs.
Only a few additional comments and illustrations of particular benefits regarding swine
will be presented.
The use of a high level of antibiotics in the diet of sows at breeding time increases concep-
tion rate and litter size. Table 33 summarizes a number of studies that involved more than
1300 sows and show an average 7% improvement in conception rate at tust estrus and 0.4
more live pigs farrowed per litter.
THE EFFECT OF ANTIBIOTICS AT BREEDING TIME
ON FARROWING RATE AND LITTER SIZE
g Rate, %
Messersmith et al., 342
Dean and Tribble, 144
Ruiz etal., 433a
Myers and Speer, 372
Mayrose et al., 323
Soma & Speer, 49 1,490
^Chlortetracycline, 0.5 to 1.0 g/sow/day.
^Chlortetracycline, 0.5 to 1.0 g/sow/day, 0.54 g/sow/day.
'^Chlortetracycline, sulfamethazine and penicillin at 0.5, 0.5 and 0.25 g/sow/day,
Tylosin phosphate, 0.6 g/sow/day.
Speer (493) summarizes additional unpublished data on both tetracycline and tylosin
which in some cases show an even larger difference in conception rate than shown in Table
33. A high level of an absorbable antibiotic seems necessary to elicit this response. This
is reasonable since conception rate or litter size problems are likely associated with sys-
temic rather than gastrointestinal problems. Using embryo survival to 28 days as an indi-
cator of reproductive performance, Sosa et^al. (492) reported that tylosin improved the
number of live embryos but that bacitracin did not. Neither of these antibiotics are
particularly well absorbed, but tylosin appears to be more effective against systemic
Young growing pigs show a markedly greater and more consistent response to antibiotics
than do more mature animals. Table 34 provides a typical illustration of the greater
response of very young pigs as compared with that of older pigs.
EFFECT OF FEEDING OLEANDOMYCIN AT DIFFERENT LEVELS
ON PERFORMANCE OF PIGS^
Pigs Tested and
Level of Olean-
Units of feed per unit of gain.
''Initial age 13 days.
Initial age 5 1 days.
Oleandomycin was fed to the two groups of pigs. In baby pigs, the antibiotic resulted in
an increase in growth rate of 30%- to 44% and an improvement in feed efficiency of 14%
to 20%. In the older pigs, the antibiotic resulted in an improvement of 7% to 10% in
growth rate and efficiency. This age effect is further illustrated by the data in Tables
5, 26 and 27.
The diets used today to evaluate the effectiveness of antibiotics are, in general, more
adequately balanced to meet the animals' needs than were the diets used in the early
1950's. There are two main reasons for this: more information is available regarding the
nutrient needs; some nutrients, particularly the vitamins, are less expensive today. The
feeding of nutritionally balanced diets reduces but does not eliminate the response to anti-
biotics. Certain developments may have offset some of the gains made possible by greater
knowledge about nutrient requirements. For example, the performance of pigs during the
starter phase in 1957 to 1966 is not as good as in 1950-1956 (see bottom of Table 5).
During the early 1950's most early weaned pigs were started on diets high in milk
products. The cost of milk products has resulted in a reduction in the use of this higlily
digestible source of protein and carbohydrate. The diet changes probably explain the
greater response in antibiotics in 1957-1966 as compared with 1950-1956. Another
illustration in the tables which should be noted is the improvement in feed/gain ratios
with time for the growing-finishing pigs. If the data is averaged for penicillin-streptomycin,
tetracyclines and bacitracin, there has been a 9.6% change in feed conversion of control
animals as compared with a 6.0% for the antibiotic treated animals. Assuming that
the genetic potential is the same for the antibiotic treated and control groups, the data
support the earlier cited observations of Waibel et d. (556) and Libby and Schaible (296)
that a portion of the reduction in percentage responses is a result of improvement of the
controls rather than a decline in the effectiveness of the antibiotic.
A statistical evaluation of the tetracychne data (120 experiments) in Table 26 revealed no
significant year by treatment interaction for feed/gain ratios. There was a significant linear
improvement in feed conversion with time (0.01 1 Ib/yr) with a constant predicted improve-
ment (P<01) of 0.10 lb. of feed per pound of gain for the treated group as compared with
controls. There was evidence of a treatment by year interaction for rate of gain. Regres-
sion analysis showed no significant change with time for the treated group, but a signifi-
cant increase in growth rate of controls to 1962 and a constant rate thereafter. The initial
difference in 1950 was about 0.2 lb. per day; this difference declined to approximately
0.08 lb/day by 1962 and remained constant thereafter. This improvement in performance
of controls relative to no change in performance of treated animals is consistent with the
previously cited observations of Waibel et _al_. (556) and Libby and Schaible (296) for
poultry. The observation was probably first expressed, but not published to my knowledge,
by the late Damon V. Catron.
The improvement in feed/gain ratios accompanied by little, if any, change in rate of gain
with time reflects the selection emphasis in the swine industry. More selection pressure
has been put on reducing fatness in pigs. This leads indirectly to a reduction in total feed
required per unit of live weight gain. This has probably had an even greater impact on
reducing feed required per unit of gain than any direct efforts to select for improved
Hygienic conditions in swine production have not greatly improved in recent years. Though
greater knowledge about the role of hygiene in animal performance has been gained and
producers are expending greater effort in this regard, other changes in systems of produc-
tion have occurred that partially offset the advances made in sanitation practices. These
changes have been necessitated by the increased value of land and a marked reduction in
available labor. Producers are finding it necessary to specialize in fewer livestock enter-
prises and to confine their animals to smaller spaces in order to release land for alternative
uses and to facilitate the mechanization of feeding and disposing of wastes.
Such intensification of production accentuates some of the environmental factors affect-
ing responses to antibiotics. The increased concentration of animals in limited space can
lead to a higher incidence of clinical and subchnical disease because of the greater ease of
transmittal. Fortunately, the use of antibiotics has contributed to the success of many of
these intensive units. Feed additive usage results in the greatest responses during periods
of natural or imposed stresses. In pigs the greatest responses are observed at breeding or
farrowing in sows, at weaning in young pigs and during the stresses associated with reloca-
tion, such as movement of feeder pigs. Similar situations apply to other species.
V. Effectiveness of Antibacterial Agents in Feeding Programs for Growing Chicks and
The factors affecting the response of chickens to antibiotics are similar to those affecting
the responses by pigs. The management programs are, however, very different. Because of
the ability to provide nearly unlimited day -old chicks at a given time, much more rigorous
control over the genetic background of the chicks, the management procedure of all-in,
all-out systems of productions, different disease and parasite problems, and the many
other differences in production procedures and problems, it is obvious that the need for
and conditions for use differ markedly between poultry and swine.
The antibacterial agents which are useful for the two species are generally the same. It
does appear that certain drugs, for example bacitracin and penicillin alone, are more effec-
tive in poultry than in swine. In swine feeding programs the application of bacitracin has
been limited primarily to the growing-finishing stage, whereas in chicks it has been used
extensively in the starter stage. Penicillin has been used very extensively in poultry feed-
ing programs; it has usually been used in combination with other drugs (streptomycin,
bacitracin, chlortetracycline, etc.) in swine feeding programs.
The examples cited illustrate the responses of growing chicks to antibacterial agents. These
responses are summarized in more detail in Table 35 for chicks to about four weeks of
age and in Table 36 for chicks to approximately eight weeks of age.
SUMMARY OF CHICK PERFORMANCE TO ABOUT 4 WEEKS
% Imp.^' n^
^ n = number of comparisons (experiments).
Percentage improvement in performance due to antibiotics.
''Average weight (g) per bird and feed/gain for birds fed diets without (-) or with (+)
'^ChJortetracycline and oxytetracycline. References: 40, 44, 48, 106, 132, 133, 140,
153a, 164, 178, 188, 192,225,227,230,282,303,307,311,314,321,361,373,393,
401, 432, 442, 450, 451, 452, 469, 489, 506, 507, 527, 539, 567, 569, 592, 593, 596.
^References: 1, 41, 60, 1 12, 132, 140, 164, 168, 170, 172, 188, 225, 227, 230, 233, 235,
261, 269, 295, 307, 314, 318, 319, 321, 352, 361,367,379,414,442,462,484,506,
^References: 41, 106, 140, 168, 169, 171, 178, 188, 225, 307, 321, 318, 319. 320, 352,
361 , 379, 392, 414, 527, 539, 567, 569, 596.
^References: 1,87, 168, 169, 171,295,320,367,400,450,461,556,591.
'^References: 140, 192, 225, 227, 261, 361.
'References: 163, 164,379.
J References: 177,368.
' References: 319, 320. 321. 352.
'"References: 133. 310. 321. 352. 561.
"References: 361. 379. 527. 596.
SUMMARY OF CHICK PERFORMANCE TO ABOUT 8 WEEKS
Number of comparisons (experiments).
Percentage improvement in performance due to antibiotic.
^Average weight (g) per bird and feed/gain for birds fed diets without (-) or with ( + ) antibiotics.
^Ciilortetracvcline and oxvtetracvcline. References: 106. 133. 141. 178. 339. 442. 450. 472.
489. 572. 573. 574. 583, 592, 5%.
'References: 42. 106. 135. 141, 178,251,319,320,321.339.414.572,574.585.
^References: 135. 141. 171. 274, 275, 295, 318, 320, 351, 354. 400,421,450, 572.
'^References: 133, 274. 275. 319, 321, 561.
J References: 368.
.•\s was the case for the comprehensive summaries of swine data, researchers do nt)t use
the same length of trials, same diets, etc. Those e.xperimeiits involving diets which greatly
exaggerate the responses were e.xcluded from these sununaries. Certain dietary ingredients
such as rye, improperly toasted soybean meal. etc.. greatly exaggerate responses to anti-
biotics. These diets may be particularly helpful in screening antibacterial agents for effec-
tiveness or the antibacterial agents may be beneficial in using such ingredients. The inclu-
sion of these experiments in the summary ct)uld give a somewhat distorted evaluation of
the overall effectiveness.
in Table 35 the weighted average of 5(i5 experiments, which involved thousands of chicks,
shows an average of 6.72 percent improvement in weights. In 31 3 of those experiments,
data were also presented for feed required per unit of gain; the average response was
4.43'/. Similar summaries to approximately iS weeks of age were 2.94''f improvement in
chick weights and 2.48'^ improvement in feed conversion (Table 36).
There are differences in final average weights for the control birds for the different anti-
biotics presented in the summary. A part of these differences in weights can be related to
the time span over which the antibiotics were tested and a part can be attributed ti) the
fact that the summaries involved both layer breeds and broiler breed chicks and for some
antibiotics a higher proportion of the experiments in the summary involved broiler breeds.
For example, the experiments with lincomycin are limited to 1974-1977, whereas the tests
with tetracyclines and penicillin cover the entire period of usage, 1950 to 1977. During the
past 27 years tremendous genetic improvements in rate of weight gain and efficiency
of feed conversion have been made, in the early 1950"s it took more than 10 weeks to
produce a 3.5 pound broiler and required 3.0 pounds of feed or more per pound of gain.
Now. it takes less than 8 weeks time and the feed conversii)n may be 2 pounds of feed
per pound of gain or less.
The mean responses presented in Tables 35 and 36 illustrate the effectiveness of the drugs
in improving bird weiglits and feed conversion.
Summaries of the percentage responses to antibiotics since 1970 in comparison with all
years are presented in Tables 37 and 38.
IMPROVliMHNT IN (HICK PERFORMANCE - ALL YEARS VS. SINCE 1970
(TO APPROXIMATELY 4 WEEKS OF AGE)^
No. '' imp.
No. ''< Imp.
^Data from Table 35.
IMPROVEMENT IN CHICK PERFORMANCE - ALL YEARS VS. SINCE 1970
(TO APPRO.XIMATELY 8 WEEKS OF AGE)^
No. % Imp.
1 1 2.93
^Data from Table 36.
There is some variation but. in general, these summaries illustrate continued etTectiveness.
There have been many changes, as discussed previously, in the industry during that time
span, and these changes can affect the magnitude of the response. To approximately 4 weeks
of age. the average response to penicillin ( 12.20 vs. 8.1 \'r) and bacitracin (7.34 vs. 6.3r7)
is higher for the time period since 1970 than for the overall period. For tetracyclines
(6.79 vs. Ijy.'t) and arsenicals (4.71 vs. 4.94^7) the trend is in the opposite direction.
For feed conversion, the average response to tetracycline (7.14 vs. 4.46%) is greater since
1970 than for the entire time span. The average feed/gain response to bacitracin (2.75 vs.
3.24%) and to arsenicals (4.81 vs. 7.01 y) is in the opposite direction. If all the environ-
mental and genetic variations that existed in these indirect time comparisons were subject
to critical evaluation, the real change in magnitude of response could possibly be deter-
mined. These data illustrate, however, the continued effectiveness of all four antibacterial
agents. Table 38 presents a similar summary for chicks to 8 weeks of age. These data are
possibly more consistent with the e.xpected change in response to antibacterial agents
over time with chicks. The progress accomplished in controlling some of the major poultry
diseases including coccidiosis. the improvements in diet formulations and the improve-
ments made in housing and ventilation should all contribute to a lower response to the
antibacterial agents; however, there is evidence of continued effectiveness. These sum-
maries are generally consistent with the conclusions of Bird (46). He limited his summary
to broiler breed chicks and to experiments which continued to market weight and con-
cluded that data t>om 1951 to 1968 did not show any trend toward decreased effective-
ness of the four antibiotics (chlortetracycline, ox\'tetracycline, penicillin and bacitracin)
having the longest history of use.
There is less data available for layer and breeder hens. Table 39 presents a summary of
SUMMARY OF ICiCi PRODUCTION.
Plil-D PI:R DOZliN LCiGS AND HATCIIABILITY
+ '/< Imp.
1 1 .9 1
''Number of comparisons of hens fed diets without (-) or with ( + ) antibiotics.
'^Chlortetracyciine and o.xytetracycline. Referencs: 10. 41. 52. 62. 90, 133. 136. 162.
226, 228. 229. 231. 404. 438. 463. 471. 528.
'^References: 10. 11. 18, 85. 136, 143, 226, 228. 295, 301, 410, 529a, 575.
^References: 41. 52. 76. 85. 91. 125a, 133, 143. 155. 156. 228. 301, 370. 404. 405,
^References: 41.86, 156, 226, 252.
Reference: 1 2>}).
^References: 136, 193. 194, 226, 382, 383, 415.
'^Ret^erences: 10, 1 1, 85. 91. 125a, 136, 143, 193, 194, 226, 228. 243. 286. 336. 387,
No attempt was made to separate time comparisons, as the available data is for the most
part limited to the early years of the introduction of antibacterial agents into the feeding
program. Most of the data on tetracvclinc and penicillin is from the 19S()'s; lor erythriv
mycin. frt)m the 19(-)0"s; and tor bambermvcin, from the l'-'70"s. In this table. 9| expeii-
ments were included in a grouping ot others plus combinations. This grouping included
drugs or combinations that were never approved plus those lor which there ma\ have
been niininnim data, and is only included to add credence to ihe othei observations that
antibacterial agents are beneficial.
The weiglited average responses to the antibacterials hsted were 4.01 , 4.72 and 3.41% for
egg production, feed required per dozen eggs and percent hatchability, respectively. Many
of the experiments were based on a full laying-year period for the egg production and
feed conversion. For hatchability, the data were frequently limited to much shorter
periods. These overall average responses included only those experiments (as was the case
for the growing data) for which the diets were formulated to be nutritionally adequate
and did not include dietary ingredients that would exaggerate the response. There is the
consistent opinion among researchers, as expressed in the literature, that the magnitude
of the response is markedly influenced by temperature, humidity and other environmental
stresses. Extreme cold weather(Ryan et a]., 438; Nivas et al., 382) or extreme hot weather
(Heywang, 228, 229, 231), which cannot be completely avoided due to year-around
production in all areas of the country, increases the response to antibiotics.
A summary of field experiments by Melliere (336) is presented in Table 40.
EFFECT OF TYLOSIN ON EGG PRODUCTION^
Hens per treatment
Feed/doz. eggs, kg.
Summary of 14 field trials, Melliere (336).
The averages of 2.0% improvement in egg production and 3.5% improvement in efficiency
of feed conversion are similar in magnitude to that of the later stages of broiler production.
VI. Effectiveness of Antibacterial Agents in Feeding Programs for Turkeys
Potter (412) summarized the response of turkeys to antibiotics to the year 1971. For the
starter period (0 to 4 weeks of age) he reported an average of 19.3 and 18.2% improve-
ment in gains and 7.3 and 7.6% improvement in feed conversions for penicillin and tetra-
cycline, respectively. To 8 weeks of age the responses were 18.1 and 16.8% improvement
in gains and 1 0.0 and 10.1% improvement in feed/gain for penicillin and tetracycline,
respectively. Potter reported on a few experiments in which the turkeys were taken to
market weight. For penicillin the average response was 5.2 and 8.6% for gain and feed/
gain response, respectively. Comparable data for tetracycline were 3.2 and -1.2%.
SuiiiiiKiry Tables 41 . 42 and 43 piesciit average responses to several anlibiolics.
RispoNsi; or turkizys to antibiotics
(TO APPROXIMATl-LY 4 WIIEKS 01 AGH)
^Number of experiments in which turkeys were ted diets without (-) or with ( + )
''References: 5. 61.116. 140. .^>03. 328. 329. 330. 361. 394. 399. 442.
""References: 61 . 116. 140. 283. 308. 328. 329. 330. 361 . 394. 442. 443. 454. 468. 476.
477^ 479. 481. 500. 558. 570, 598.
"^References: 105. 116. 206. 361, 363, 419, 442, 454, 516, 559. 568.
"^References: 61. 140. 283, 328, 330, 361, 394, 559.
RESPONSE OF TURKEYS TO ANTIBIOTICS
(TO APPROXIMATELY 8 WEEKS OF AGE)
'^Number of experiments in which turkeys were fed without (-) or with ( + ) antibiotics.
'^Chiortetracycline and oxytetracycline. References: 6, 12, 13, 61, 399, 453, 482, 483.
515, 554, 588.
^^References: 13,61. 266,309,442.444,473,482, 515,589.
^References: 19,413,417.419,420, 515,516, 555,562,586.
^16 weeks of age rather than 8. Reference: 355.
RESPONSE OF TURKEYS TO ANTIBIOTICS
(TO MARKET WEIGHT)
^Number of experiments in which turkeys were fed diets without (-) or with ( + )
'^References: 309, 444, 473. 476. 481 .
^'References: 19, 252,310,413.418,419. 513.555.
The average responses are similar to those reported by Potter. The average weight responses
were 13.3. 7.0 and 1 .2f< I'or data to 4 weeks. 8 weeks and market weigiit (20 to 24
weeks), respectively. Feed/gain icsponses were 7.0. 3.8 and 1 .9 for the same periods.
Responses of egg production, feed/egg and hatchabilily are presented in Table 44.
EFFECTS OF ANTIBIOTICS ON RATE AND EFFICIENCY OF
EGG PRODUCTION AND HATCHABILITY IN TURKEYS''
Egg production, 7c
''References; 14, 16, 19, 88, 142. 474, 557.
Turkey hens fed diets without (-) or with ( + ) antibiotics.
Egg production was improved by 1.36% and feed/egg improved by 6.407f. Data available
from 16 experiments indicate that antibiotics have little or no effect on hatchabilily. This
differs from the results with chickens in which hatchability was improved an average of
VII. Effects of Antibiotics On Mortality and Morbidity
There is much less published data available on mortality and morbidity than for rate and
efficiency o^ gain. Most of the swine reports do not include such data, probably because
of the relatively small number of animals per experiment. Maddock (312) summarized a
series of field experiments involving the antibacterial combination of chlorletracycline,
sulfamethazine and penicillin and reported that 3.17% of the control pigs died as compared
with 2.21% of the treated pigs. Those figures are based on 49 separate experiments involv-
ing 2,204 pigs. Table 30 includes mortality data for several antibiotic comparisons. The
average mortality for the control groups was 5.1% as compared with 1.8% for the anti-
biotic treated group, based on 274 pigs per group. For the experiments presented in
Table 10, the experimental records show mortality figures of 8.5% for the control groups
and 3.8% for the treated groups. These experiments involved a total t)f 616 pigs.
White-Stevens and Zeibel (583) reported the mortality and condemnation rates for a
large group of broilers (5,000 per treatment) on a farm where chronic respiratory disease
was a recognized problem. Including chlortetracycline (100 g/ton) in the diet reduced
mortality (2.8 vs. 10.7%), reduced culling or condemnation (0.1 vs. 1.3%), increased
weight of birds (3.08 vs. 2.87 lb.) and markedly increased the total marketed weiglUs
(14,933 vs. 12,4001b.).
A number of papers (02, 297, 2b}. 318, 351 . 35^). 365, 387, 404, 405, 410, 415, 438,
440, 4b3) include data on mortality: the general trend is toward a reduction in mortality
from having antibiotic in the teed. In most experimental situations, mortality is relatively
low and the researchers are usually nt)t in a position to attribute mortality or survival to
a specific dietary treatment and do not anticipate that their experiments will be included
in a large summary in an attempt to assess average mortality.
Antibiotic feed supplements have now been used routinely and successfully in livestock
and poultry priiduction for more than 27 years. As the worldwide demand for animal
protein increases, the use of antibacterial agents will bectime increasingly important for
maintaining an efficient and competitive livestock industry. Tlicre can be no doubt that
antibiotics continue to provide substantial economic benefits to both the producer and
consumer of meat, milk and eggs.
The number of alternative antibiotics which have been proven etTective in improving per-
formance is relatively small. These antibiotics are those often found to be most effective
in treatment o\' diseases. This observation is ct>nsistent with the evidence which supports
the thesis that antibiotics result in improved performance through their control or preven-
tion of specific or nimspecific diseases. These observations are significant since one is not
likely to find antibiotics that are both particularly usefiil in improving performance oi"
animals and that have no application in treatment of diseases. Additives other than anti-
bacterial may result in improved rate and efficiency of gain. However, since their mode
of action will likely be ditTerent, these additives will not replace or substitute tor anti-
The magnitude of the response to antibacterial agents varies with stage of life cycle, stage
of production and the environmental conditions to which the animals are exposed. The
response is greater in young animals than in more mature animals. The response is greater
during critical stages of production such as weaning, breeding, farrowing, or immediately
post hatching in chicks and turkeys. Environmental stresses such as inadequate nutrition,
crowding, moving and mi.xing of animals, poor sanitation and high or low temperatures
also contribute to increased responses. Such stresses are ordinary and to a large degree
A critical review of the average responses to the various antibacterial agents clearly
indicates that there are marked differences in the magnitude and consistency of responses.
In general, those with a broader spectrum of antibacterial activity and those that are
effective against gram-negative bacteria result in the greatest and most consistent responses.
Comparisons of the responses to antibacterial agents in recent years with responses in
the early penod of use demonstrate that those extensively used are still of benefit in
improving growth rate and efficiency. There is some evidence that the magnitude of the
response has declined for some uses. In view of the progress in nutrition, housing, manage-
ment, sanitation and other factors that affect the response to antibiotics, it is surprising
that the decline is not greater. There is also evidence that consistent use of antibiotics
results in actual improvement in performance of the control animals rather than regres-
sion of treated groups.
IX. Research Needs
The development of antibiotic resistance with loss in efficacy and possible compromise
of therapy in humans and animals has been a primary concern since the introduction of
antibiotics, it has been proposed that meat, milk and eggs from animals fed antibiotics
contribute to the transterable drug resistance in the consumer. This assumption could be
tested with proper interspecies experimentation. Carel'ul epicleiiiiological studies are
needed to determine the source of antibiotic resistance in humans and to what degree
that resistance originates in animals and their flora. Interspecies studies excluding humans
could provide more satisfactt)ry evidence than is available now. but animal-to-human and
human-to-human transfer studies are needed.
There is evidence that resistance development and resistance transfer may be reduced or
prevented by concurrent use of other drugs. The safety and efficacy of these should be
fully studied. Llse of such drugs could lead to continued application of present drugs and
could also extend or increase their therapeutic efficacy.
Further research is needed to determine if chronic oral exposme of humans to antibiotics
and low-level, feed-additive usage in animals compromises therapy in humans or animals.
Even after extensive use of the tetracyclines and penicillin, they continue to be the pri-
mary drugs of choice for prophylactic and therapeutic use. A restriction in prophylactic
or feed additive usage would likely increase therapeutic use, leading to total use at or
above the present level. There is a need to determine whether therapeutic use or low level
is the major contributor to resistance levels.
The modes of action for antimicrobial agents are still an area of major disagreement, it is
recognized that animals are exposed to a very complex and ever-changing microflora; thus
the specific modes of action may be complex and ever-changing. Little research effort has
been devoted to the determination of the modes of action. This research could lead to
alternative drugs or methods.
A thorough evaluation of the relative efficacy of currently available and new drugs is
needed. Data on the older drugs permit indirect comparisons of the relative etTects on
performance, mortality and morbidity; much less data are available for direct compari-
sons. Greater emphasis on field evaluation of antibiotics is needed. Numerous environ-
mental factors which affect the response to antibiotics cannot be adequately simulated in
a laboratory situation. It is possible only through field evaluation to accurately assess the
economic impact from use or restriction of use of antibiotics on animal production.
Considerable research has been devoted to the possible detrimental effects of drug use in
animals on human health. There has been, however, little attention to the possible bene-
ficial effects of antibiotic usage in animals on human health. Reduction in infections,
abscesses, etc., may be of benefit to man and should be investigated.
Finally, research should be continued on metlu)ds of improving performance of animals
without the use of drugs. Genetic resistance to disease, immunization to disease organisms
and improved environment are all possible means of circumventing the need for anti-
microbial drugs in animal production systems.
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